Insulin and sulfonylurea compounds such as tributamide and Glipizide have been used as therapeutic agents for diabetes and hyperglycemia, the use of phenylalkylcarboxylic acid derivatives for treatment of non-insulin-dependent diabetes was recently reported. These compounds include, for example.
(1-1) 3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]-2-(acetylthio)propion ic acid and its esters, 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]propionic acid, 3-[[4-(4-benzyloxyphenyl)ethoxy]phenyl]-2-methoxypropionic acid, 2-phenoxy-3-[4-(2-phenyl)ethoxyphenyl]propionic acid and the like are disclosed in PCT Publication No. WO91/19702 (Japanese PCT Application (Kokai) No. Hei 5-507920).
(1-2) 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-((N-ethyl-N-phe nyl)amino)propionic acid and its esters and the like are disclosed in PCT Publication No. WO94/29285.
(1-3) 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-pyrrolepropioni c acid and its esters and the like are disclosed in PCT Publication No. WO94/29302.
(1-4) 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-(propyl)propion ic acid and its esters, 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-(3-phenylpropyl )propionic acid and its esters, 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-(3-methylbutyl) propionic acid and its esters and the like are disclosed in PCT Publication No. WO95/03288.
(1-5) 3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]phenyl]-2-(2,2,2-trifluor oethoxy)propionic acid and its esters and the like are disclosed in PCT Publication No. WO96/04260.
Moreover, the use of a large number of thiazolidine derivatives has recently been reported as therapeutic agents for the treatment of non-insulin-dependent diabetes. These compounds include, for example,
(2-1) 5-[4-[(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)methoxy]benzyl]-2,4-thiaz olidinedione (International Non-proprietary Name (INN): Troglitazone) is disclosed in U.S. Pat. No. 4,572,912, EP 139421A and Japanese Patent Publication (Kokoku) No. 2-31079.
(2-2) 5-[[4-[2-(5-ethyl-pyridin-2-yl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione (INN: Pioglitazone) is disclosed in EP 8203A, U.S. Pat. No. 4,287,200, U.S. Pat. No. 4,340,605, U.S. Pat. No. 4,438,141, U.S. Pat. No. 4,444,779, U.S. Pat. No. 4,725,610, Japanese Patent Publication (Kokoku) No. Sho 62-42903 and Japanese Patent Publication (Kokoku) No. Hei 5-66956.
(2-3) 5-[[3,4-dihydro-2-(phenylmethyl)-2H-benzopyran-6-yl]methyl]-2,4-thiazolidi nedione (INN: Englitazone) is disclosed in U.S. Pat. No. 4,703,052 and Japanese Patent Publication (Kokoku) No. Hei 5-86953.
(2-4) 5-[[4-[2-[N-methyl-N-(pyridin-2-yl)amino]ethoxy]phenyl]methyl]-2,4-thiazol idinedione (Code Designation: BRL-49653) is disclosed in EP 306228A, U.S. Pat. No. 5,002,953, U.S. Pat. No. 5,194,443, U.S. Pat. No. 5,232,925, U.S. Pat. No. 5,260,445 and Japanese Patent Application (Kokai) No. Hei 1-131169.
The relationships between these compounds and various diseases are described in the following references with respect to, for example, thiazolidine derivatives.
The effects of thiazolidine derivatives on hyperglycemia are described in (1) Diabetes., 32(9), 804-810 (1983); (2) Diabetes., 37(11), 1549-1558 (1988); (3) Prog. Clin. Biol. Res., 265, 177-192 (1988); (4) Metabolism., 37(3), 276-280 (1988); (5) Arzneim.-Forsch., 40(1), 37-42 (1990); (6) Arzneim.-Forsch., 40(2, Pt. 1), 156-162 (1990); and, (7) Arzneim.-Forsch., 40(3), 263-267 (1990).
The effects of thiazolidine derivatives on hyperlipemia are reported in (1) Diabetes., 40(12), 1669-1674 (1991); (2) Am. J. Physiol., 267(1, Pt. 1), E95-E101 (1994); and (3) Diabetes., 43(10), 1203-1210 (1994).
The effects of thiazolidine derivatives on impaired glucose tolerance and insulin resistance are reported in (1) Arzneim.-Forsch., 40(2, Pt. 1), 156-162 (1990); (2) Metabolism., 40(10), 1025-1030(1991); (3) Diabetes., 43(2), 204-211 (1994); and, (4) N. Engl. J. Med., 331(18), 1226-1227 (1994).
The effects of thiazolidine derivatives on hypertension are reported in (1) Metabolism., 42(1), 75-80 (1993); (2) Am. J. Physiol., 265(4, Pt. 2), R726-R732 (1993); and, (3) Diabetes., 43(2), 204-211 (1994).
The effects of thiazolidine derivatives on cachexia are reported in (1) Endocrinology., 135(5), 2279-2282 (1994); and, (2) Endocrinology., 136(4), 1474-1481 (1995).
The effects of thiazolidine derivatives on nephropathy are reported in (1) Diabetes., 38 (Special Edition), (1995) (38th Annual Technical Meeting of the Japan Diabetes Society, Program Proceedings, 38th Meeting of the Japan Diabetes Society, 1995).
The effects of thiazolidine derivatives on coronary artery disease are reported in (1) Am. J. Physiol., 265(4, Pt. 2), R726-R732 (1993); and, (2) Hypertension., 24(2), 170-175 (1994).
The effects of thiazolidine derivatives on arteriosclerosis are reported in (1) Am. J. Physiol., 265(4, Pt. 2), R726-R732 (1993).
Moreover, it has recently been reported in (1) N. Engl. J. Med., 331(18), 1226-1227 (1994) that normal individuals having insulin resistance unaccompanied with glucose intolerance have a high risk for the onset of diabetes (referred to as "insulin-resistant non-IGT: NGT"). It is suggested that medicaments which can improve insulin resistance would be useful as preventive drugs against the onset of diabetes in normal individuals like those described above.
However, the compounds mentioned above are different from the compounds of the present invention in that they do not have an oxime bond in their side chain, while the compounds of the present invention have the oxime bond in their side chain.
Incidentally, compounds which have an oxime bond in their side chain and are non-insulin-dependent agents for the treatment of diabetes that have effects similar to those described above, have been disclosed after the date of claiming the priority of the present application. These compounds include, for example, aromatic oximino derivatives such as (4-1) 5-[4-[2-[(4-hydroxyindan-1-yl)iminoxy]ethoxy]benzyl]-2,4-thiazolidinedione , 5-[4-[2-[(2,3-dihydro-6-phenylbenzofuran-3-yl)iminoxy]ethoxy]benzyl]-2,4- thiazolidinedione, 5-[4-[2-[(5-chloroindan-1-yl)iminoxy]ethoxy]benzyl]-2,4-thiazolidinedione, 5-[4-[2-[(5-methylindan-1-yl)iminoxy]ethoxy]benzyl]-2,4-thiazolidinedione, 5-[4-[2-[(5,6-methylenedioxyindan-1-yl)iminoxy]ethoxy]benzyl]-2,4-thiazoli dinedione, 5-[4-[2-[(5-phenylindan-1-yl)iminoxy]ethoxy]benzyl]-2,4-thiazolidinedione and they are disclosed in PCT Publication No. WO96/38427 (publication date: Dec. 5, 1996) and Japanese Patent Application (Kokai) No. Hei 9-48770 (publication date: Feb. 18, 1997); oxime derivatives such as (4-2) 5-[4-[2-[[[1-(4-biphenylyl)ethylidene]amino]oxy]ethoxy]benzyl]thiazolidine -2,4-dione, 5-[4-[2-[[[1-[4-(2-pyridyl)phenyl]ethylidene]amino]oxy]ethoxy]benzyl]thiaz olidine-2,4-dione, 5-[4-[2-[[[1-(2-phenyl-5-pyridyl)ethylidene]amino]oxy]ethoxy]benzyl]thiazo lidine-2,4-dione, 5-[4-[2-[[[1-(2-methoxy-5-pyridyl)ethylidene]amino]oxy]ethoxy]benzyl]thiaz olidine-2,4-dione are disclosed in EP 708098A (publication date: Apr. 24, 1996) and Japanese Patent Application (Kokai) No. Hei 9-48779 (publication date: Feb. 18, 1997).